Safety of Spironolactone in Dogs with Chronic Heart Failure because of Degenerative Valvular Disease: A Population‐Based, Longitudinal Study

Abstract

Background: Spironolactone treatment in humans is associated with an increased risk of hyperkalemia and renal dysfunction.Hypothesis: Dogs with cardiac disease treated with spironolactone, in addition to conventional therapy, are not at higher risk for adverse events (AEs) than those receiving solely conventional therapy.Animals: One hundred and ninety-six client-owned dogs with naturally occurring myxomatous mitral valve disease. Methods: Prospective, double-blinded field study with dogs randomized to receive either spironolactone (2 mg/kg once a day) or placebo in addition to conventional therapy (angiotensin-converting enzyme inhibitor, plus furosemide and digoxin if needed). Safety was compared between treatment groups, using the frequency of AEs, death caused by cardiac disease, renal disease, or both, and variations in serum sodium, potassium, urea, and creatinine concentrations. For the latter, population-specific reference intervals were established and out of range values (ORV) analyzed.Results: The number of AEs was similar in the spironolactone and reference groups (188 and 208, respectively), when followed for median duration of 217 days (range [2-1,333]). At each study time point, the percentage of dogs showing ORV was similar between groups. There were a higher number of deaths because of cardiac disease, renal disease or both in the reference group (30.7% versus 13.7%) (P = .0043).Conclusions and Clinical Importance: Dogs with heart failure receiving spironolactone in addition to conventional treatment are not at a higher risk for AEs, death caused by cardiac disease, renal disease, or both, hyperkalemia, or azotemia.

Treatment of dogs with compensated myxomatous mitral valve disease with spironolactone—a pilot study

“…There was a tendency for serum potassium concentrations to be higher in dogs treated with spironolactone at baseline and the 2 week time point. Nevertheless, all measurements remained within the range of normal values and so this is not a source of pharmacovigilance concern nor has it been noted as a clinically significant adverse event in the published clinical trials involving spironolactone in dogs [25].…”

The renin‐angiotensin‐aldosterone system and its suppression

“…A safety analysis of dogs involved in the study of Bernay and colleagues showed that those receiving spironolactone, in addition to standard treatment (including an ACEI), were not at higher risk for adverse events (such as death from renal disease and abnormalities in serum sodium, potassium, urea nitrogen, and creatinine), when compared with dogs receiving placebo and standard treatment . In fact, mortality caused by cardiac disease, kidney disease, or both was lower in the group treated with spironolactone.…”

Short‐Term Efficacy and Safety of Torasemide and Furosemide in 366 Dogs with Degenerative Mitral Valve Disease: The TEST Study

“…Benefits of ACE inhibitors, pimobendan, and spironolactone in DMVD dogs with CHF have been demonstrated. In all these prospective randomized controlled clinical trials, furosemide was authorized and prescribed in most (66%) to all recruited dogs .…”